Lung Cancer Awareness Month 2020

Transcript

00:00 --> 00:02Support for Yale Cancer Answers
00:02 --> 00:05comes from AstraZeneca, committed to
00:05 --> 00:08pioneering the next generation of
00:08 --> 00:10innovative lung cancer treatments.
00:10 --> 00:14Learn more at astrazeneca-us.com.
00:14 --> 00:16Welcome to Yale Cancer Answers with
00:16 --> 00:18your host doctor Anees Chagpar.
00:18 --> 00:20Yale Cancer Answers features the
00:20 --> 00:22latest information on cancer care by
00:22 --> 00:24welcoming oncologists and specialists
00:24 --> 00:26who are on the forefront of the
00:26 --> 00:28battle to fight cancer. This week,
00:28 --> 00:30it's a conversation about lung
00:30 --> 00:31cancer with Doctor Sarah Goldberg.
00:31 --> 00:33Doctor Goldberg is an associate
00:33 --> 00:35professor of internal medicine and
00:35 --> 00:37medical oncology at the Yale School
00:37 --> 00:39of Medicine where Doctor Chagpar
00:39 --> 00:41is a professor of surgical oncology.
00:42 --> 00:45Sarah, maybe we can start off
00:45 --> 00:48by talking about lung cancer.
00:48 --> 00:50I mean when many people think
00:50 --> 00:53about lung cancer, they think of it
00:53 --> 00:55as kind of a devastating disease.
00:55 --> 00:58Tell us a little bit more
00:58 --> 01:00about how many people get it,
01:00 --> 01:02who gets it, and historically,
01:02 --> 01:04what has been the prognosis?
01:04 --> 01:06So lung cancer is
01:06 --> 01:07a very common cancer.
01:07 --> 01:09It's the second most common cancer
01:09 --> 01:11in the US among both men and women.
01:11 --> 01:14But you're right, it absolutely can be a
01:14 --> 01:16devastating illness and because of that,
01:16 --> 01:19it's the number one cause of cancer deaths
01:19 --> 01:21among both men and women.
01:21 --> 01:23So it's common, and it's a common
01:23 --> 01:24cause of death from cancer.
01:24 --> 01:27But I think a lot has changed
01:27 --> 01:28in recent years.
01:28 --> 01:31I know we'll talk about a lot of that,
01:31 --> 01:33but some of the things that we've
01:33 --> 01:36known for a long time now is that
01:36 --> 01:38people tend to be older when
01:38 --> 01:39they get lung cancer,
01:39 --> 01:41although some people are quite young.
01:41 --> 01:43Smoking is a risk factor for lung cancer,
01:43 --> 01:44but again,
01:44 --> 01:45some people have never smoked
01:45 --> 01:48a day in their life and they
01:48 --> 01:49can still get the disease.
01:53 --> 01:54Does genetics play into it?
01:54 --> 01:56I mean on this show we talk a
01:56 --> 01:58lot about genetics as well,
01:58 --> 01:59but when it comes to lung cancer,
02:00 --> 02:01most of us think that this
02:01 --> 02:03is really a smoking related cancer.
02:03 --> 02:05Although as you say there are
02:05 --> 02:07people who never smoked a day in
02:07 --> 02:09their life who get lung cancer.
02:09 --> 02:11So for them, is it really genetics?
02:11 --> 02:12What's an underlying
02:12 --> 02:13cause for that?
02:13 --> 02:14There's a lot about lung cancer
02:14 --> 02:16that we still don't know.
02:16 --> 02:18And your question is a great one,
02:18 --> 02:20and it's something that we still don't
02:20 --> 02:21fully understand about lung cancer
02:21 --> 02:25because smoking is such a common risk
02:25 --> 02:29factor for lung cancer.
02:29 --> 02:30When we see someone who's smoked,
02:30 --> 02:33who gets lung cancer, we think that it's
02:33 --> 02:35probably related in some way.
02:35 --> 02:37But again, when people have never smoked,
02:37 --> 02:38we really don't understand the cause
02:38 --> 02:40for the vast majority of those cancers.
02:41 --> 02:42When you think of
02:42 --> 02:44genetics in terms of
02:44 --> 02:45inheriting a gene from your parents
02:45 --> 02:47or passing it along to kids,
02:47 --> 02:49that's not really common at all
02:49 --> 02:50in lung cancer like it is in
02:50 --> 02:52other cancers like breast cancer,
02:52 --> 02:54which tends to be more common.
02:54 --> 02:56We just don't see that very
02:56 --> 02:57much in lung cancer,
02:57 --> 02:59so why some people who have never
02:59 --> 03:01smoked get it is still really
03:01 --> 03:03an outstanding question in the field.
03:03 --> 03:05There are some other environmental risks,
03:05 --> 03:06but much,
03:06 --> 03:08much lower than the risk of smoking.
03:08 --> 03:11So secondhand smoke is also a risk,
03:11 --> 03:13but again, much lower.
03:13 --> 03:16Radon is always a question.
03:16 --> 03:18There probably is some risk there,
03:18 --> 03:20but how to quantify that?
03:20 --> 03:21It is very difficult,
03:21 --> 03:24so for many people who haven't
03:24 --> 03:27smoked or haven't smoked much,
03:27 --> 03:28it's still very unclear
03:28 --> 03:30why they get this disease.
03:30 --> 03:32You know the other thing
03:32 --> 03:35that we talked about in a lot
03:35 --> 03:37of different cancers is that any
03:37 --> 03:39particular cancer lung cancer,
03:39 --> 03:40breast cancer, colon cancer,
03:40 --> 03:42whatever, it is rarely one disease, is
03:42 --> 03:44lung cancer like that as well?
03:44 --> 03:47Or are all lung
03:47 --> 03:49cancers essentially the same?
03:49 --> 03:52So this is one of the things that
03:52 --> 03:54I think is the most interesting and
03:54 --> 03:56probably exciting about lung cancer.
03:56 --> 03:59Up until a couple years ago we really
03:59 --> 04:01thought there were two types of lung cancer,
04:02 --> 04:04small cell and non small cell lung cancer.
04:04 --> 04:06But over the last really 10 or 15 years
04:06 --> 04:08it's become clear that it's multiple
04:08 --> 04:11diseases that are all labeled as lung
04:11 --> 04:13cancer because of where it started,
04:13 --> 04:15where the cancer started in the lung.
04:15 --> 04:17And this is one of the biggest advances
04:17 --> 04:20in the field over the last several years
04:20 --> 04:22is the understanding of the different
04:22 --> 04:25types of lung cancer and it's not just so
04:25 --> 04:28that we can define things in a different way.
04:28 --> 04:29It's really because it impacts treatment
04:29 --> 04:31and how well different cancers
04:31 --> 04:33respond to different treatments.
04:33 --> 04:34How well someone is going to
04:34 --> 04:36do with various treatments,
04:36 --> 04:37and so differentiating these
04:37 --> 04:39different types of lung cancers is
04:39 --> 04:41absolutely critical so that we can
04:41 --> 04:42get the best treatments for patients.
04:42 --> 04:44We still do think about small
04:44 --> 04:46cell and non small cell,
04:46 --> 04:48but mostly within the realm of non
04:48 --> 04:50small cell lung cancer is where
04:50 --> 04:51we've been able to divide things
04:51 --> 04:53up even more and understand
04:53 --> 04:58mostly the molecular basis of lung cancer.
04:58 --> 05:00Meaning that the cancer has different
05:00 --> 05:01mutations and that is really
05:01 --> 05:03part of what defines it.
05:03 --> 05:06Now you just asked me about mutations and I
05:06 --> 05:09said it's not very common in lung cancer,
05:09 --> 05:11but I'm talking about a different
05:11 --> 05:12type of mutation here,
05:12 --> 05:15so it's not very common that people have
05:16 --> 05:18a genetic predisposition to lung cancer.
05:18 --> 05:20But finding mutations in the cancer
05:20 --> 05:21itself is actually quite common.
05:22 --> 05:24Yeah, we've had
05:24 --> 05:27other guests on the show here as well who
05:27 --> 05:30talk about this concept where
05:30 --> 05:33a biopsy is taken and the tumor is
05:33 --> 05:35profiled for a number of mutations,
05:35 --> 05:38genetic mutations that it could
05:38 --> 05:40have that could tailor
05:40 --> 05:43therapy and it sounds like lung cancer
05:43 --> 05:46is in that realm as well.
05:46 --> 05:48Tell us more about the mutations
05:48 --> 05:52that you look for and the sub
05:52 --> 05:54classifications that you think about
05:54 --> 05:56when you're treating a lung cancer
05:56 --> 05:57patient.
05:57 --> 05:59Lung cancer is a great example
05:59 --> 06:02of a disease where the molecular
06:02 --> 06:04classifications are so important,
06:04 --> 06:06and so whenever we see a patient
06:06 --> 06:09with a non small cell lung cancer,
06:09 --> 06:10that's advanced
06:10 --> 06:12meaning at stage four, it's critical
06:12 --> 06:14to get molecular or mutation testing.
06:14 --> 06:17People will call it different things.
06:17 --> 06:18Molecular testing, mutation testing.
06:18 --> 06:20Tumor profiling is sometimes used,
06:20 --> 06:22and so that is now entirely a standard
06:22 --> 06:25part of treatment and what's really
06:25 --> 06:28changed over the years is what we
06:28 --> 06:30need to test and
06:30 --> 06:32when I first started in this field
06:32 --> 06:34now 10 years ago there was really
06:34 --> 06:36just one mutation that we can target
06:36 --> 06:38and that was the EGFR mutation and
06:38 --> 06:40that was so exciting at the time
06:41 --> 06:42because it was really the first
06:42 --> 06:44time in lung cancer that we could
06:44 --> 06:47get a biopsy as you say and do the
06:47 --> 06:49mutation testing and if we found this
06:49 --> 06:51mutation we had a great treatment
06:51 --> 06:53which is a targeted therapy pill,
06:53 --> 06:55EGFR inhibitor and that is still the
06:55 --> 06:57case today where we're looking for
06:57 --> 06:59EGFR mutations and we will target
06:59 --> 07:00those cancers with pills that treat
07:00 --> 07:02that specific abnormality in the cancer.
07:03 --> 07:05Some people will call it targeted therapy
07:05 --> 07:06or precision or personalized medicine,
07:06 --> 07:08but now instead of just one
07:08 --> 07:10mutation that we can target,
07:10 --> 07:12we have several that have been
07:12 --> 07:14discovered in lung cancer that have
07:14 --> 07:15associated targeted therapies.
07:15 --> 07:17So we've really come a
07:17 --> 07:19long way in just a couple of years
07:19 --> 07:21where now we don't test one,
07:21 --> 07:23but we test many genes because we
07:23 --> 07:26may be able to find a mutation
07:26 --> 07:27that is important in that
07:27 --> 07:29cancer.
07:29 --> 07:31Tell us the other mutations that you
07:31 --> 07:33look for.
07:33 --> 07:35Thinking about a timeline, so ALK was probably
07:35 --> 07:38the next one that was discovered.
07:38 --> 07:41Alk is a mutation in a gene that
07:41 --> 07:43again can be part of a lung cancer,
07:43 --> 07:45especially lung adenocarcinomas.
07:45 --> 07:47Most of these mutations really all
07:47 --> 07:49these mutations are mostly found in
07:49 --> 07:51adenocarcinomas, which is a type
07:51 --> 07:53of non small cell lung cancer.
07:53 --> 07:56And so ALK is another mutation like the
07:56 --> 07:59EGFR mutation where if we find it
07:59 --> 08:02I get very excited for patients because
08:02 --> 08:04we have fantastic therapies for Alk.
08:04 --> 08:05So that's another one.
08:05 --> 08:07It's rare, ALK rearrangements are found
08:07 --> 08:10in just a couple percent of lung cancers.
08:10 --> 08:11But again,
08:11 --> 08:12absolutely critical to look for because
08:12 --> 08:14of the great options for treatment,
08:14 --> 08:16we have another another gene that
08:16 --> 08:18we always test is called RAS one,
08:18 --> 08:20and that also can have a mutation
08:20 --> 08:22in it and the list keeps going on.
08:22 --> 08:25So that was really all we had
08:25 --> 08:26for a couple of years.
08:26 --> 08:27But really,
08:27 --> 08:29in the last I would say year or two,
08:29 --> 08:31there's been even more of
08:31 --> 08:32discovery of alterations,
08:32 --> 08:33so now we always will need to
08:33 --> 08:35assess for BRAF mutations.
08:35 --> 08:37BRAF is a gene that
08:37 --> 08:39commonly has mutations in Melanoma,
08:39 --> 08:41but more recently was also found
08:41 --> 08:43to have mutations in lung cancers.
08:43 --> 08:45Again just a couple of percent of
08:45 --> 08:47lung cancers have BNRAF mutations,
08:47 --> 08:48but now we have targeted therapies
08:48 --> 08:51that we can use for that and then
08:51 --> 08:53really recently within just the last
08:53 --> 08:55couple of months or year we look at
08:55 --> 08:57MET mutations and ntrk mutations,
08:57 --> 08:59RET I might have forgotten a couple
08:59 --> 09:01there's getting to be so many.
09:02 --> 09:04We have now several new FDA
09:04 --> 09:05approvals for these
09:05 --> 09:06targeted therapies,
09:06 --> 09:09but if you don't know the mutation is there,
09:09 --> 09:11you're not going to use the drug,
09:11 --> 09:13so it's really become very
09:13 --> 09:14important to test even
09:14 --> 09:16more than ever before.
09:16 --> 09:18And you mentioned
09:18 --> 09:19that this is standard,
09:19 --> 09:21but you've mentioned now
09:21 --> 09:23at least half a
09:23 --> 09:25dozen mutations that you look for.
09:25 --> 09:27So is that something that
09:27 --> 09:29is standard of care?
09:29 --> 09:30So any of our listeners,
09:30 --> 09:32no matter where they go,
09:32 --> 09:34whether they go to
09:34 --> 09:36a large academic Cancer
09:36 --> 09:38Center or whether they go to
09:38 --> 09:40a local private practice oncologist,
09:40 --> 09:43is that something that is going
09:43 --> 09:46to be tested for them for
09:46 --> 09:48their lung cancer across the
09:48 --> 09:50board and across the country?
09:50 --> 09:53Or is this still something that really
09:53 --> 09:56hasn't found its way out of academe
09:56 --> 09:58yet?
09:58 --> 10:00It absolutely should be standard of care
10:00 --> 10:02because we have FDA approved therapies
10:02 --> 10:05when you find one of these targets
10:05 --> 10:06that aren't useful unless the
10:06 --> 10:08target is there and you don't know
10:08 --> 10:11to use it unless you find it so,
10:11 --> 10:12this should be part of standard
10:12 --> 10:14of care for every patient,
10:14 --> 10:15no matter where they are.
10:15 --> 10:17The testing is available anywhere.
10:18 --> 10:20We do the testing in house,
10:20 --> 10:21so our pathology Department is fantastic.
10:21 --> 10:23They do the testing here, but there's
10:23 --> 10:25companies that do this testing now,
10:25 --> 10:28so it is available anywhere in the US.
10:28 --> 10:30It's a matter of whether it's done,
10:30 --> 10:33and I think that's the bigger question,
10:33 --> 10:34so I think now,
10:34 --> 10:36because EGFR mutations have been
10:36 --> 10:38part of the standard testing,
10:38 --> 10:40you really have to test for EGFR mutations,
10:40 --> 10:43and that's been for 2004 was
10:44 --> 10:46when the mutation was first discovered,
10:46 --> 10:47so we've
10:47 --> 10:49known about EGFR mutations
10:49 --> 10:50for well over a decade.
10:50 --> 10:53I think that's become very standard to
10:53 --> 10:55test and then the other ones I mentioned,
10:55 --> 10:57initially, Alk and RAS,
10:57 --> 10:59those have become more common because
10:59 --> 11:01they've been around for awhile too.
11:02 --> 11:03But the other ones that I
11:03 --> 11:05mentioned are equally important.
11:05 --> 11:07The issue is that there are more
11:07 --> 11:09recent so that sometimes
11:09 --> 11:10things take longer to catch on,
11:10 --> 11:12and they're also really rare,
11:12 --> 11:15so each one of the other ones I mentioned,
11:16 --> 11:18are no more than 2% of lung adenocarcinomas,
11:18 --> 11:20so they are rare but really
11:20 --> 11:21important to test for,
11:21 --> 11:23so I would hope and expect that they
11:23 --> 11:26are being tested in every patient with
11:26 --> 11:27an advanced form of adenocarcinoma,
11:27 --> 11:30but I suspect that that's not always
11:30 --> 11:32happening because of the rarity of them,
11:32 --> 11:33and because it's
11:33 --> 11:34a relatively
11:34 --> 11:36recent advance in lung cancer,
11:36 --> 11:38but they should be tested.
11:38 --> 11:40Now we actually test for a whole
11:40 --> 11:42lot of other genes at Yale,
11:42 --> 11:44and I think that a lot of
11:44 --> 11:45other academic centers,
11:45 --> 11:47so that part is maybe not as necessary.
11:47 --> 11:49You know, we test for
11:49 --> 11:52at least 50 genes at Yale and some of
11:52 --> 11:54that is trying to think about clinical
11:54 --> 11:57trials for patients and other things,
11:57 --> 11:57but those,
11:57 --> 11:58as you said,
11:58 --> 12:00more than half a
12:00 --> 12:01dozen genes are standard care.
12:01 --> 12:03Obviously, important to test for
12:03 --> 12:05and is that covered by insurance?
12:05 --> 12:07I mean, is that expensive?
12:07 --> 12:09I'm kind of trying
12:09 --> 12:12to think of this from the standpoint of
12:12 --> 12:14our listeners who may have lung cancer,
12:14 --> 12:17may have family members or friends
12:17 --> 12:19who have been recently diagnosed
12:19 --> 12:21and who may not have known to ask.
12:21 --> 12:25You know what is my ALK status, you know?
12:25 --> 12:27Do I have a RAS
12:27 --> 12:29mutation and so you know,
12:29 --> 12:32in broaching that subject, one of the
12:32 --> 12:35issues that always comes up is number one,
12:35 --> 12:37what is the cost and #2,
12:37 --> 12:39is it covered by my insurance?
12:39 --> 12:41And then of course #3,
12:41 --> 12:44can I really avail myself of the therapies?
12:44 --> 12:46But we'll get to the
12:46 --> 12:48therapies part in a moment.
12:48 --> 12:50What about the testing?
12:50 --> 12:52Is it covered or not covered?
12:52 --> 12:53Is it expensive?
12:53 --> 12:55If people haven't been tested,
12:55 --> 12:57can they get their own specimens and
12:57 --> 13:00send them off to some lab that can do
13:00 --> 13:02a commercial test if they so wanted?
13:02 --> 13:03How does that all work?
13:04 --> 13:06Right, so because the testing
13:06 --> 13:08and the treatment is standard of
13:08 --> 13:10care and approved by the FDA,
13:10 --> 13:12it's covered by insurance,
13:12 --> 13:13so these tests are expensive.
13:13 --> 13:15It's all genetic testing DNA
13:15 --> 13:17sequencing things like that
13:17 --> 13:19but it's covered it's standard,
13:19 --> 13:20so it's covered by insurance.
13:20 --> 13:24So in terms of if someone could just go,
13:24 --> 13:26you know, do their own testing,
13:26 --> 13:29the nice thing is
13:29 --> 13:31that once you've had a biopsy,
13:31 --> 13:34it goes to the lab and it stays there
13:34 --> 13:36for as far as I understand, decades.
13:36 --> 13:38So if someone
13:38 --> 13:39asked their oncologist,
13:39 --> 13:42have I had this test and the answer is no.
13:42 --> 13:44Actually we didn't test for all these.
13:44 --> 13:45It's not like all is lost.
13:45 --> 13:47You can still test it.
13:47 --> 13:48So I think that has to be
13:48 --> 13:49done from the doctor's office
13:49 --> 13:51and the pathology Department,
13:51 --> 13:53but it absolutely could be done
13:53 --> 13:54even years after
13:54 --> 13:55a diagnosis is made.
13:55 --> 13:57Well, we're going to dig more into
13:57 --> 13:59what happens after you have that
13:59 --> 14:00information in terms of treatment,
14:00 --> 14:02right after we take a short
14:02 --> 14:03break for medical minute.
14:03 --> 14:04Please stay tuned to learn
14:04 --> 14:06more about lung cancer with my
14:06 --> 14:07guest doctor Sarah Goldberg.
14:07 --> 14:10Support for Yale Cancer Answers
14:10 --> 14:12comes from AstraZeneca,
14:12 --> 14:16an industry leader in the development of
14:16 --> 14:18breakthrough immunooncology therapies across
14:18 --> 14:21multiple tumor types and stages of cancer.
14:21 --> 14:24Learn more at astrazeneca-us.com.
14:24 --> 14:27This is a medical minute about Melanoma.
14:27 --> 14:29While Melanoma accounts for only
14:29 --> 14:31about 4% of skin cancer cases,
14:31 --> 14:33it causes the most skin cancer
14:33 --> 14:35deaths. When detected early,
14:35 --> 14:37however, Melanoma is easily treated
14:37 --> 14:39and highly curable. Clinical
14:39 --> 14:41trials are currently underway to test
14:41 --> 14:43innovative new treatments for Melanoma.
14:43 --> 14:46The goal of the specialized programs
14:46 --> 14:48of research excellence in skin cancer
14:48 --> 14:51or SPORE grant is to better understand
14:51 --> 14:54the biology of skin cancer with a focus
14:54 --> 14:56on discovering targets that will lead
14:56 --> 14:59to improved diagnosis and treatment.
14:59 --> 15:01More information is available
15:01 --> 15:02at yalecancercenter.org.
15:02 --> 15:07You're listening to Connecticut Public Radio.
15:07 --> 15:07Welcome
15:07 --> 15:09back to Yale Cancer Answers.
15:09 --> 15:12This is doctor Anees Chagpar and I'm
15:12 --> 15:14joined tonight by my guest doctor
15:14 --> 15:16Sarah Goldberg and we're talking about
15:16 --> 15:19lung cancer and right before the break
15:19 --> 15:21Sarah was telling us about how lung
15:21 --> 15:24cancer is actually a much more complex
15:24 --> 15:26disease than we thought previously.
15:26 --> 15:29No longer do we think about it just as
15:29 --> 15:32small cell and non small cell but really,
15:32 --> 15:34lung cancer has burgeoned into
15:34 --> 15:36a whole plethora of of diseases
15:36 --> 15:38based on genetic mutations
15:38 --> 15:42of the cancer itself that can be profiled
15:42 --> 15:44and potentially targeted for therapies,
15:44 --> 15:47and this testing, while expensive,
15:47 --> 15:49is covered by insurance.
15:49 --> 15:52Sarah the one question I wanted
15:52 --> 15:55to pick up on just before we
15:55 --> 15:58move on to the treatments,
15:58 --> 16:01which I think is going to be super
16:01 --> 16:05interesting, is what about for our
16:05 --> 16:07non insured uninsured patients?
16:07 --> 16:10It's great that the testing
16:10 --> 16:12is covered by insurance,
16:12 --> 16:15but if somebody doesn't have
16:15 --> 16:16insurance as many,
16:16 --> 16:19many American patients don't,
16:19 --> 16:21what are their
16:21 --> 16:21alternatives?
16:21 --> 16:24Yeah, lack of insurance is
16:24 --> 16:26difficult in a lot of different ways,
16:26 --> 16:28not just with testing.
16:28 --> 16:30It also comes down to doctors
16:30 --> 16:31visits and treatment too,
16:31 --> 16:33so I think that's something
16:35 --> 16:37that we sometimes see and
16:37 --> 16:39we work
16:39 --> 16:41very closely with
16:41 --> 16:43multiple people to try
16:43 --> 16:45to to work on these issues,
16:45 --> 16:46especially our social workers
16:46 --> 16:48and try to make every effort to
16:48 --> 16:50get people the care that they
16:50 --> 16:52need in whatever way possible,
16:52 --> 16:53whether that's helping them
16:53 --> 16:55find insurance or figure out
16:55 --> 16:56other resources
16:56 --> 16:58because it's such an important part
16:58 --> 17:01of care to get this testing done.
17:01 --> 17:03I think that kind of is wrapped
17:03 --> 17:04up in the whole
17:04 --> 17:06issue with diagnosis and
17:06 --> 17:08then finding the right treatment.
17:08 --> 17:10It's all part of that.
17:10 --> 17:12So typically were able to find
17:12 --> 17:14a way to cover this in some
17:14 --> 17:15capacity for patients.
17:16 --> 17:18We could do a whole show on all
17:18 --> 17:21of the implications of having so many
17:21 --> 17:23millions of Americans being uninsured,
17:23 --> 17:25and what that does for
17:25 --> 17:27the health of our nation,
17:27 --> 17:29but that's another show.
17:29 --> 17:32Let's turn to a happier topic,
17:32 --> 17:36which is now that we have an
17:36 --> 17:39understanding of all of these mutations
17:39 --> 17:42that every cancer can exhibit,
17:42 --> 17:46we now can figure out what
17:46 --> 17:50makes one cancer different from another.
17:50 --> 17:52And once we can figure out
17:52 --> 17:55what makes a cancer tick,
17:55 --> 17:56we can potentially
17:56 --> 17:59stop it from ticking through personalized
17:59 --> 18:01therapies and targeted agents that
18:01 --> 18:03can really address these pathways.
18:03 --> 18:07So can you talk a little bit about
18:07 --> 18:09what we know and what are some of
18:09 --> 18:12the exciting drugs that
18:12 --> 18:15address each of these mutations?
18:16 --> 18:17Sure, so as you mentioned,
18:17 --> 18:19there's many different exciting
18:19 --> 18:21drugs for the various mutations,
18:21 --> 18:22and each one generally
18:22 --> 18:24does the same thing.
18:24 --> 18:26It tries to block the activity of
18:26 --> 18:28the abnormal mutation that's
18:30 --> 18:32causing the cancer
18:32 --> 18:33cell to grow and be abnormal.
18:33 --> 18:35And if you could block that,
18:35 --> 18:37it could be extremely effective,
18:37 --> 18:40and so that's true regardless of which of
18:40 --> 18:43these mutations are found in the cancer.
18:43 --> 18:46EGFR is a great example,
18:46 --> 18:48because we've known about it
18:48 --> 18:50for the most amount of time,
18:50 --> 18:52there was an EGFR inhibitor
18:52 --> 18:54that we used initially called erlotinib
18:54 --> 18:56and if that was really effective.
18:56 --> 18:59But over the years we've realized
18:59 --> 19:01that other EGFR inhibitors that have
19:01 --> 19:03been developed since then are even
19:03 --> 19:05more effective and seemed to work in
19:05 --> 19:07more people and work for longer,
19:07 --> 19:09because one thing that I haven't
19:09 --> 19:11mentioned is that these drugs,
19:11 --> 19:13while they can be extremely effective and
19:13 --> 19:14help people,
19:15 --> 19:18and shrink the cancer and work for a long,
19:18 --> 19:20long time when the cancer is at
19:20 --> 19:21an advanced stage,
19:21 --> 19:23it's not curable so the drugs can work
19:23 --> 19:26and again they can work for years.
19:26 --> 19:28But at some point the cancer gets smarter
19:28 --> 19:30and grows despite these targeted therapies.
19:30 --> 19:33So as we've developed newer and better drugs,
19:33 --> 19:34they tend to work for longer,
19:34 --> 19:36and so that's really what we're
19:36 --> 19:39trying to do is find drugs that work
19:39 --> 19:41for a really long time and make this
19:41 --> 19:43cancer a chronic disease that people
19:43 --> 19:45may not be able to cure or get
19:45 --> 19:47rid of entirely,
19:47 --> 19:48but they can live
19:48 --> 19:50with it for a long time,
19:50 --> 19:52and so in each of the different
19:52 --> 19:54targeted therapy realms for each
19:54 --> 19:55mutation we have great examples
19:55 --> 19:57of drugs that can give people
19:57 --> 19:59many more years of life than they
19:59 --> 20:01otherwise would have had.
20:01 --> 20:03And with each of these drugs, though
20:03 --> 20:05there's presumably side effects,
20:05 --> 20:08what does that look
20:08 --> 20:09like?
20:09 --> 20:12Any drug can have its share of
20:12 --> 20:14side effects and it's variable
20:14 --> 20:16depending on the drug, but overall,
20:16 --> 20:17the targeted therapies tend to
20:17 --> 20:19have less side effects than kind
20:19 --> 20:21of our classic cancer drugs,
20:21 --> 20:22mainly chemotherapy because
20:22 --> 20:23they're targeted and aimed
20:23 --> 20:24specifically at the mutation.
20:24 --> 20:26That's the abnormality in the
20:26 --> 20:28cancer cells which doesn't exist
20:28 --> 20:30in other cells,
20:30 --> 20:32in the normal cells in the body.
20:32 --> 20:33The non cancer cells.
20:33 --> 20:35The mutation is not there,
20:35 --> 20:37so the drugs don't tend to bother
20:37 --> 20:39the normal cells quite as much
20:39 --> 20:40as with chemotherapy.
20:40 --> 20:42So again, every drug is different.
20:42 --> 20:43Some of the more common ones
20:43 --> 20:45that we sometimes see is rash,
20:45 --> 20:46sometimes people are more
20:46 --> 20:48tired than they usually are,
20:48 --> 20:50but generally they are much better tolerated.
20:50 --> 20:52So it's almost like a win win.
20:52 --> 20:54They work better than other cancer therapies,
20:54 --> 20:56and they have less side effects,
20:56 --> 20:57so again,
20:57 --> 20:58we find one of these mutations
20:58 --> 21:00that we can target in a patient.
21:00 --> 21:03I am very excited and I think
21:03 --> 21:04hopefully my enthusiasm catches
21:04 --> 21:06on to the page with the patient
21:06 --> 21:07and they get very excited too,
21:07 --> 21:09especially once they see how well
21:09 --> 21:12it works. Now you know when people
21:12 --> 21:13are talking about therapies,
21:13 --> 21:15I mean on the one hand,
21:15 --> 21:17clearly they're really excited about
21:17 --> 21:19these really effective therapies
21:19 --> 21:21that last a really along time,
21:21 --> 21:24but the other thing is that they don't
21:24 --> 21:26really want to come to the hospital
21:26 --> 21:29and have an IV infusion of a therapy.
21:29 --> 21:31And when people think about chemotherapy,
21:31 --> 21:34that's what they think about they think
21:34 --> 21:36about being in the infusion suite,
21:36 --> 21:38hooked up to an IV
21:38 --> 21:40losing their hair and getting nauseous,
21:40 --> 21:41and repeating that cycle
21:41 --> 21:44multiple times, so are these therapies
21:44 --> 21:46IV, or are they oral?
21:46 --> 21:50How well do they fit into peoples lives?
21:50 --> 21:53Especially if we're talking about
21:53 --> 21:56taking them for a long time
21:56 --> 21:58and making what was previously
21:58 --> 22:01thought of as a fatal disease,
22:01 --> 22:05more of a chronic one that you can live
22:05 --> 22:09with rather than die from.
22:12 --> 22:13The IV treatments are challenging because
22:13 --> 22:15people usually have to
22:15 --> 22:17come in fairly frequently for them,
22:17 --> 22:18and you spend time here instead
22:18 --> 22:20of where you want to be.
22:20 --> 22:21These drugs are all pills,
22:21 --> 22:23so that does make it a really nice
22:23 --> 22:26part of it is that you take your
22:26 --> 22:28daily pill or twice a day pill like you
22:28 --> 22:30would take your blood pressure pills
22:30 --> 22:33and you don't need to come into the
22:33 --> 22:35hospital nearly as often as an IV medicine.
22:35 --> 22:37I will say that
22:37 --> 22:40as exciting as all of this is,
22:40 --> 22:41and hopefully you can
22:41 --> 22:43sense my enthusiasm for it,
22:43 --> 22:44it still is only
22:44 --> 22:48maybe about 20 or 25% of patients
22:48 --> 22:50with lung cancer that we can find one
22:50 --> 22:53of these mutations that we can target.
22:53 --> 22:55So the numbers are
22:55 --> 22:58going up as we find more mutations,
22:58 --> 22:59but it's still unfortunately
22:59 --> 23:02not everyone and so
23:02 --> 23:04there's been a huge amount of work in
23:04 --> 23:06other areas of lung cancer where
23:06 --> 23:08we can't find a targetable mutation,
23:08 --> 23:10and then the other end
23:10 --> 23:12that's mainly with immune therapies.
23:14 --> 23:16What about the other 75% of people?
23:16 --> 23:17What's in their cancer
23:17 --> 23:19if they don't have targetable mutations,
23:19 --> 23:21and what can we do about that?
23:21 --> 23:24So I think those two areas are so
23:24 --> 23:25critical as well because we
23:26 --> 23:28haven't come far enough to
23:28 --> 23:29figure out a targeted therapy
23:29 --> 23:31strategy for every patient yet.
23:31 --> 23:33And I think that both of those
23:33 --> 23:35issues are are so critical.
23:35 --> 23:37Let's dig into those.
23:37 --> 23:40But before we get there,
23:40 --> 23:42these targeted therapies are,
23:42 --> 23:44for example, in breast cancer we
23:44 --> 23:46have targeted therapies as well,
23:46 --> 23:48which often are given in
23:48 --> 23:49combination with chemotherapy.
23:49 --> 23:51But it sounds like these targeted
23:51 --> 23:54therapies can be used as sole agents.
23:54 --> 23:55Is that right?
23:55 --> 23:56That's right. Yes.
23:56 --> 23:59There is some research going
23:59 --> 24:02on trying to combine them with chemotherapy,
24:02 --> 24:04but you're right at this point,
24:04 --> 24:06the way we use them is
24:06 --> 24:07the targeted therapy alone.
24:07 --> 24:09They've been really in almost
24:09 --> 24:10every case
24:10 --> 24:12there's been trials comparing the targeted
24:12 --> 24:14therapy compared to chemotherapy,
24:14 --> 24:16and it's superior in all the cases.
24:16 --> 24:18Again, when you have the target
24:18 --> 24:19and use the targeted therapy,
24:19 --> 24:21it's better than using chemotherapy,
24:21 --> 24:24and we haven't found a reason to combine it,
24:24 --> 24:25although there again,
24:25 --> 24:27is some research looking at
24:27 --> 24:29if combining it is beneficial.
24:29 --> 24:31The standard is to use the
24:31 --> 24:32targeted therapy alone.
24:33 --> 24:35It's really nice for a logistic point of
24:35 --> 24:38view and side effect point of view as well.
24:38 --> 24:40Yeah, I mean that's so exciting,
24:41 --> 24:44it does kind of sound like if
24:44 --> 24:47you've got one of these mutations, you can
24:47 --> 24:50take a pill and
24:50 --> 24:53have fewer side effects and a better
24:53 --> 24:55outcome than being hooked up to chemo.
24:55 --> 24:57And you can take your pills on
24:57 --> 25:00vacation with you to wherever you're
25:00 --> 25:02going to go and live your life.
25:02 --> 25:05And it sounds like that is just so
25:05 --> 25:07exciting in terms of an advance,
25:07 --> 25:09but it does bring us to the
25:09 --> 25:11question of what if you're not
25:11 --> 25:14in one of those lucky groups that
25:14 --> 25:16has a known targetable mutation,
25:16 --> 25:17you mentioned immunotherapy.
25:17 --> 25:21You know we've talked on this show
25:21 --> 25:23about immunotherapy a little bit,
25:23 --> 25:26and I'd like to dig into
25:26 --> 25:27immunotherapy for lung cancer.
25:27 --> 25:30But the one thing that some have
25:30 --> 25:33found is that for some cancers,
25:33 --> 25:36they actually still will look for
25:36 --> 25:39a checkpoint in order to use a
25:39 --> 25:41checkpoint inhibitor just to
25:41 --> 25:44see what people's PDL1 status is.
25:44 --> 25:46But in other cancers,
25:46 --> 25:48that isn't necessarily something
25:48 --> 25:50that necessarily plays into whether
25:50 --> 25:53or not you can use immune therapy.
25:53 --> 25:56So how does it work in
25:56 --> 25:58lung cancer?
25:58 --> 26:00This has been a huge area of research over the last few years
26:00 --> 26:03in lung cancer and other cancers.
26:03 --> 26:04As you mentioned, in lung cancer,
26:04 --> 26:07we have now started using immune therapy,
26:07 --> 26:08for I would say almost every
26:08 --> 26:10patient with advanced cancer.
26:10 --> 26:11Again stage four cancer who does
26:11 --> 26:13not have one of those mutations
26:13 --> 26:15that we were talking about before.
26:15 --> 26:17Again, if you have one of the mutations
26:17 --> 26:19targeted therapies are great options,
26:20 --> 26:21but otherwise typically immune therapy
26:21 --> 26:24is going to be some part of the
26:24 --> 26:25treatment because of how effective
26:25 --> 26:27it can be and your question about
26:27 --> 26:29the PD L1 status in lung cancer
26:29 --> 26:31is really important.
26:31 --> 26:33So just like we get those mutation tests
26:33 --> 26:35and it's so important for patients
26:35 --> 26:37to find the best treatment for them.
26:37 --> 26:40It's the same with PD L1 status.
26:40 --> 26:42So PD L1 is not a mutation or gene
26:42 --> 26:45like we were talking about with the
26:45 --> 26:47other area in lung cancer treatments.
26:47 --> 26:49But it's a protein on the surface
26:49 --> 26:51of cells of cancer cells or of
26:51 --> 26:52immune system cells.
26:52 --> 26:53But in lung cancer,
26:53 --> 26:56we look at the cancer cells and
26:56 --> 26:58that protein PDL1
26:58 --> 27:00can tell us if immune therapy
27:00 --> 27:02is more or less likely to work.
27:02 --> 27:05So it's not a perfect test by any means.
27:05 --> 27:06I've had patients where the
27:06 --> 27:08PD L1 status is zero,
27:08 --> 27:09which tells you it has a
27:09 --> 27:11low chance of working.
27:11 --> 27:11However,
27:11 --> 27:12they've done incredibly well
27:12 --> 27:13with immune therapy,
27:13 --> 27:15and sometimes it's high and the
27:15 --> 27:17drugs doesn't seem to work,
27:17 --> 27:19so it's not a perfect biomarker.
27:19 --> 27:21But we do use it as part of
27:21 --> 27:22standard treatment in lung cancer,
27:22 --> 27:24and so when I meet a new patient
27:24 --> 27:26with lung cancer again at Stage 4,
27:26 --> 27:27advanced form of lung cancer,
27:27 --> 27:29we always will check mutations in PDL1
27:30 --> 27:31and the reason really is if someone
27:31 --> 27:33has a high level of that PDL1
27:33 --> 27:35marker we think we might be able
27:35 --> 27:37to get away with just giving immune
27:37 --> 27:38therapy just like we were
27:38 --> 27:40talking about with targeted therapy,
27:40 --> 27:41how it's nice to avoid the
27:41 --> 27:42chemotherapy if you can.
27:42 --> 27:44It's the same thing with immune
27:44 --> 27:46therapy with a high level of PDL1
27:46 --> 27:48there's a high chance of the immune
27:48 --> 27:49therapy working even on its
27:49 --> 27:51own, so we will try that
27:52 --> 27:54instead of giving chemotherapy
27:54 --> 27:55or other medicines.
27:56 --> 28:00And so if you are PDL1 low and
28:00 --> 28:02you don't have another targeted
28:02 --> 28:04over another targetable mutation,
28:04 --> 28:06those patients are more likely to
28:06 --> 28:08get chemotherapy, but they'll still
28:08 --> 28:10get the immunotherapy as well.
28:15 --> 28:17Therapy can work so well we will
28:17 --> 28:21typically give it no matter what,
28:21 --> 28:23unless there's a contraindication.
28:23 --> 28:25If someone has an underlying
28:25 --> 28:26autoimmune disorder
28:26 --> 28:28but yes, if someone has that low PDL1
28:28 --> 28:30status or we don't know PDL1 status
28:30 --> 28:33then we don't think and this is based
28:33 --> 28:35on several different clinical trials.
28:35 --> 28:37We don't think we can get away with
28:37 --> 28:39just immune therapy on its own and
28:39 --> 28:40it seems to be much more effective
28:40 --> 28:42if you combine it with something else
28:42 --> 28:44and that something else is a
28:44 --> 28:46bit of a question mark in lung cancer.
28:46 --> 28:48Until recently it used to be we
28:48 --> 28:49would combine it with chemotherapy
28:49 --> 28:51so people would get a combination
28:51 --> 28:53of chemo and immune therapy.
28:53 --> 28:54But more recently now based on
28:54 --> 28:55several recent clinical trials,
28:55 --> 28:57we're actually combining two
28:57 --> 28:58different immune therapies together.
28:58 --> 28:59So avoiding chemotherapy,
28:59 --> 29:00but combining the immune therapies.
29:00 --> 29:03And that's an area of future research
29:03 --> 29:05that is currently ongoing.
29:05 --> 29:07We have several different
29:07 --> 29:09clinical trials at Yale
29:09 --> 29:10looking at these different
29:10 --> 29:11combinations of immune therapy.
29:11 --> 29:14Really trying to get away from the
29:14 --> 29:16chemotherapy if we can and using
29:16 --> 29:18combinations of immune therapy to
29:18 --> 29:20really try to beat the cancer and
29:20 --> 29:22really try to improve patients
29:22 --> 29:24quality of life and how long they
29:24 --> 29:25are able to live.
29:27 --> 29:29Doctor Sarah Goldberg is an associate professor of internal
29:29 --> 29:31medicine in medical oncology at
29:31 --> 29:33the Yale School of Medicine.
29:33 --> 29:34If you have questions,
29:34 --> 29:36the address is canceranswers@yale.edu
29:36 --> 29:38and past editions of the program
29:38 --> 29:40are available in audio and written
29:40 --> 29:41form at yalecancercenter.org.
29:41 --> 29:44We hope you'll join us next week to
29:44 --> 29:47learn more about the fight against
29:47 --> 29:49cancer here on Connecticut Public Radio.

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November 8, 2020

Yale Cancer Center

visit: http://www.yalecancercenter.org

email: canceranswers@yale.edu

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